The purpose of this project is to elucidate the neural mechanisms and principles of treatment of chronic pain syndromes. We are conducting a placebo-controlled study of the new anticonvulsant topiramate in chronic lumbar radiculopathy pain. A new program in pain genetics has localized a gene affecting pain behaviors to a small region of one chromosome containing several genes whose gene products have previously been linked to pain processing. Candidate gene studies are beginning in a cohort of 500 patients with 10-year followup of sciatica in the Maine Lumbar Spine Study. Extramural collaborations include a collaboration with Johns Hopkins in which morphine treatment was superior to tricyclic antidepressant treatment in patients with postherpetic neuralgia, the first direct comparison of these two standard treatments.